Optimal frequency-based weighting for spectral x-ray projection imaging.
The purpose of this work is to derive a weighting scheme that maximizes the frequency-dependent ideal observer signal-difference-to-noise ratio, commonly referred to as detectability index or Hotelling-SDNR, for spectral X-ray projection imaging. Starting from basic statistical decision theory, optimal frequency-dependent weights are derived for a multiple-bin system and the Hotelling-SDNR calculated. A 28% increase in detectability index is found for high frequency objects when applying optimal frequency-dependent weights instead of pixel-based weights to a simplified model of a silicon detector, decreasing towards 0% for low frequency objects. Simulation results indicate a potentially large increase in detectability for high-frequency object imaging using silicon detectors, thus meriting further evaluations on a real system.


Botulinum toxin therapy for cervical dystonia: the science of dosing.
The first-line treatment for cervical dystonia (CD) is botulinum toxin type A (BoNT-A), which has been established as a highly effective and well-tolerated therapy. However, this treatment is also complex and challenging to apply in clinical practice. Approximately 20% of patients discontinue therapy due to treatment failure, adverse effects, and other reasons. In addition, expert consensus recommendations are lacking to guide physicians in the optimal use of BoNT-A for CD. Among the issues still to be clarified is the optimal dosing frequency. The generally accepted standard for intervals between BoNT-A injections is ≥12 weeks; however, this standard is based primarily on the methodology of pivotal trials for the BoNT-A products, rather than on evidence that it is optimal in comparison to other intervals. While some retrospective, observational studies of BoNT-A used in clinical practice appear to support the use of ≥12-week dosing intervals, it is often unclear in these studies how the need for reinjection was determined. In contrast, a prospective dose-ranging trial in which patients were allowed to request reinjection as early as 8 weeks showed that about half of patients receiving abobotulinumtoxinA, at the currently recommended initial dose of 500 U, requested reinjection at 8 weeks. Moreover, results from an open-label, 68-week extension phase of the pivotal trial of incobotulinumtoxinA showed that 47.1% of patients had received reinjection at ≤12 weeks. Ongoing studies, such as the Cervical Dystonia Patient Registry for Observation of BOTOX® Efficacy (CD PROBE), may help clarify this question of optimal dosing intervals for BoNT-A in CD.


Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.
Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.


Structure Identification of Uncertain Complex Networks Based on Anticipatory Projective Synchronization.
This paper investigates a method to identify uncertain system parameters and unknown topological structure in general complex networks with or without time delay. A complex network, which has uncertain topology and unknown parameters, is designed as a drive network, and a known response complex network with an input controller is designed to identify the drive network. Under the proposed input controller, the drive network and the response network can achieve anticipatory projective synchronization when the system is steady. Lyapunov theorem and Barbǎlat's lemma guarantee the stability of synchronization manifold between two networks. When the synchronization is achieved, the system parameters and topology in response network can be changed to equal with the parameters and topology in drive network. A numerical example is given to show the effectiveness of the proposed method.


[Surgical correction of the rheumatic concomitant mitral-aortal failure complicated by thrombosis of the left auricle].
The results of surgical treatment of 51 patients with the thrombosis of the left auricle (LA), occurred after performance of intervention for the rheumatic concomitant mitral-aortal failure (RCMAF) of the heart were analyzed. The substitution of two valves was performed in 37 patients, valve-preserving operations in combination with the prosthesis--in 14. The massive thrombosis of LA (more than 1/3 volume) occurred in 16 (31%) patients. On the hospital stage 17 patients, mainly with complicated current and organic failure of the tricuspid valve in combination with the adhesive pericarditis, calcinosis of the valves, and also previously operated for the heart, died. The late results (from 1 to 12 yrs) of intervention were studied in 33 patients. Good result was noted in 20 (60.6%) patients, satisfactory--in 5 (15.2%), nonsatisfactory--in 1 (9.1%). 5 (15.2%) patients died mainly because of the thromboembolic complications. The thromboembolic complications were not noted in patients to whom the valve-preserving procedures were conducted. All the patients in this group are alive.


Type I interferons regulate susceptibility to inflammation-induced preterm birth.
Preterm birth (PTB) is a leading worldwide cause of morbidity and mortality in infants. Maternal inflammation induced by microbial infection is a critical predisposing factor for PTB. However, biological processes associated with competency of pathogens, including viruses, to induce PTB or sensitize for secondary bacterial infection-driven PTB are unknown. We show that pathogen/pathogen-associated molecular pattern-driven activation of type I IFN/IFN receptor (IFNAR) was sufficient to prime for systemic and uterine proinflammatory chemokine and cytokine production and induction of PTB. Similarly, treatment with recombinant type I IFNs recapitulated such effects by exacerbating proinflammatory cytokine production and reducing the dose of secondary inflammatory challenge required for induction of PTB. Inflammatory challenge-driven induction of PTB was eliminated by defects in type I IFN, TLR, or IL-6 responsiveness, whereas the sequence of type I IFN sensing by IFNAR on hematopoietic cells was essential for regulation of proinflammatory cytokine production. Importantly, we also show that type I IFN priming effects are conserved from mice to nonhuman primates and humans, and expression of both type I IFNs and proinflammatory cytokines is upregulated in human PTB. Thus, activation of the type I IFN/IFNAR axis in pregnancy primes for inflammation-driven PTB and provides an actionable biomarker and therapeutic target for mitigating PTB risk.


Molecular analysis of potential hinge residues in the inactivation gate of brain type IIA Na+ channels.
During inactivation of Na+ channels, the intracellular loop connecting domains III and IV is thought to fold into the channel protein and occlude the pore through interaction of the hydrophobic motif isoleucine-phenylalanine-methionine (IFM) with a receptor site. We have searched for amino acid residues flanking the IFM motif which may contribute to formation of molecular hinges that allow this motion of the inactivation gate. Site-directed mutagenesis of proline and glycine residues, which often are components of molecular hinges in proteins, revealed that G1484, G1485, P1512, P1514, and P1516 are required for normal fast inactivation. Mutations of these residues slow the time course of macroscopic inactivation. Single channel analysis of mutations G1484A, G1485A, and P1512A showed that the slowing of macroscopic inactivation is produced by increases in open duration and latency to first opening. These mutant channels also show a higher probability of entering a slow gating mode in which their inactivation is further impaired. The effects on gating transitions in the pathway to open Na+ channels indicate conformational coupling of activation to transitions in the inactivation gate. The results are consistent with the hypothesis that these glycine and proline residues contribute to hinge regions which allow movement of the inactivation gate during the inactivation process of Na+ channels.


Diagnosis clusters adapted for ICD-9-CM and ICHPPC-2.
An ad hoc committee of the North American Primary Care Research Group (NAPCRG) was appointed to adapt the diagnosis clusters instrument for use with the International Classification of Diseases (ICD-9-CM) and the International Classification of Health Problems in Primary Care (ICHPPC-2). This article describes the development and testing of the final roster of 110 diagnosis clusters for family physicians. Almost 90 percent of all diagnoses recorded by family physicians in a variety of settings were included in the clusters. The diagnosis clusters can be used in the analysis of large databases and facilitate comparisons between different providers and practices.


Internal Medicine Resident Adherence to Evidence-Based Practices in Management of Diabetes Mellitus.
Diabetic preventative health maintenance involves (1) adherence to guidelines and (2) appropriate documentation. This study evaluates the frequency with which internal medicine (IM) residents met these two outcomes. We also evaluated if there were differences in outcomes between resident classes. In this retrospective analysis, 234 diabetic outpatient visits were analyzed. Guidelines were derived from the American Diabetes Association (ADA). The outcomes for each guideline were averaged and stratified by resident class. Averages within and between classes were compared using the student's paired t-test and one-way ANOVA respectively. Classes were most adherent to A1c testing guidelines (PGY-1 96.1%, PGY-2 97.6%, and PGY-3 95.9%). PGY-1 and PGY-2 classes were least adherent to podiatry (27.5% and 17.6% respectively), whereas PGY-3 had equal least adherence rates to podiatry and lifestyle modification guidelines (36.7%). All classes had highest rates in documenting A1c findings (PGY-1 92.2%, PGY-2 97.6%, and PGY-3 85.7%) and lowest rates in documenting relevant podiatry information (PGY-1 5.9%, PGY-2 5.9%, and PGY-3 11.2%). Comparing sequential resident classes, there was a decline in lifestyle counselling and documentation from PGY-1 to PGY-2. From PGY-2 to PGY-3, there was improvement in adherence to statin, podiatry, microalbuminuria, and monofilament guidelines. There was also improvement in documenting statin and monofilament usage, however, A1c reporting declined. The findings of the study suggest disproportionate levels of care in diabetes preventative management. Additionally, program directors should take caution in assuming linear improvement with sequential resident classes.


Factors Affecting Physical Activity of People with Knee Osteoarthritis in Southern Taiwan: A Multiple Logistic Regression Analysis.
Physical activity (PA) is a basic and initiative conservative management for people with knee osteoarthritis (KOA). This study aimed to explore the potential indicators of PA levels in people with KOA. We designed a cross-sectional study where people with KOA were consecutively approached by the Orthopedic Outpatient Department in a hospital in southern Taiwan. People older than 50 years that could communicate and consent to the present study were enrolled. As a dependent variable, the Chinese version of the Physical Activity Scale for the Elderly (PASE-C) was used to assess the participant's PA levels. Considering differences in sex, a PASE-C score cut-off point of 140 for men and 120 for women was used. Participants were then divided into "active" and "inactive" groups. We measured independent variables consisting of the demographic and clinical characteristics, such as comorbidities measured by the Charlson Comorbidity Index (CCI), depression status measured by the Geriatric Depression Scale-5, body mass index, KOA history (<5, 5-<10, and ≥10 years), knee pain (unilateral or bilateral), the severity of symptoms measured by the Western Ontario and McMaster Universities Osteoarthritis Index, and 6-meter preferred walking speed. Multiple logistic regression was performed to identify significant relationships between PA among people with KOA. We analyzed a total of 188 people with KOA (56 men and 132 women) with a mean age of 69.4 ± 7.9 (range: 51 to 90 years). Approximately 72.9% (n = 137) were categorized as "inactive PA," while 27.1% (n = 51) of participants were categorized as "active PA" (male: 32.1%; female: 25.0%). Multiple logistic regression showed a positive association of 6-meter preferred walking speed with active PA (OR: 7.08; 95% CI:1.14-44.13), whereas advanced age and comorbidity (CCI≥1 vs. CCI<1) were negatively associated with active PA with an OR (95% CI) score of 0.91 (0.86-0.97) and 0.37 (0.15-0.87), respectively. People with KOA require appropriate lifestyle management to increase PA. Walking speed may be an effective factor for predicting PA among people with KOA. Healthcare providers treating KOA patients should be aware of their PA levels, especially those at risk.


Sensorimotor adaptation modifies action effects on sensory binding.
Previous studies have shown that performing a motor action toward a target decreases the perceptual asynchrony observed in a temporal order judgment (TOJ) of a change in the target's visual attributes. We examined the temporal limit of this effect and whether this temporal limit can be extended through sensorimotor adaptation. Participants performed a TOJ task related to changes of the position and color of a visual stimulus in a perceptual and a motor task. A fixed change (color or position) occurred 250 or 500 ms following an auditory cue (perceptual task) or the end of a manual reaching action (motor task), whereas the variable change (position or color) occurred randomly within a time window of ±200 ms locked to the fixed change. The points of subjective simultaneity (PSSs) revealed that performing a voluntary action decreased the temporal asynchrony observed in the perceptual task, but only in the 250-ms delay condition. In Experiment 2, the fixed change occurred 1 s after either an auditory cue or the end of a manual reaching action, and the variable change occurred either simultaneously (new sensorimotor contingencies, 60 % of trials) or within a time window of ±200 ms (40 % of trials). The PSSs revealed that temporal asynchrony decreased in the motor task, but only after adaptation to the 1-s delay. Taken together, these data show that voluntary motor action affects the temporal binding of visual attributes for a period of less than 500 ms after the end of the action. Sensorimotor adaptation can nevertheless extend this time interval, at least up to 1 s.


Inhibition of initial adhesion of uropathogenic Enterococcus faecalis to solid substrata by an adsorbed biosurfactant layer from Lactobacillus acidophilus.
The potency of the Lactobacillus acidophilus RC14 biosurfactant "surlactin" to reduce the initial adhesion of Enterococcus faecalis 1131 was investigated on a hydrophilic and a hydrophobic substratum in a parallel-plate flow chamber, using phosphate-buffered saline and pooled human urine as a suspending fluid. A parallel-plate flow chamber with a glass or silicone rubber bottom plate was filled with different biosurfactant solutions of 0, 0.01, 0.1, or 1.0 mg/mL for overnight adsorption (18 hours). Subsequently, the adhesion of E. faecalis on thus prepared biosurfactant layers was observed in situ in phosphate-buffered saline or in urine by automated image analysis. Adsorbed biosurfactant layers caused an important, dose-related inhibition of the initial deposition rate of E. faecalis and the number of adherent bacteria after 4 hours on both hydrophilic glass and hydrophobic silicone rubber, although this effect was stronger in buffer than in urine. For the experiments carried out in urine, the inhibitory effect of the biosurfactant layer was largest when silicone rubber was used rather than glass, whereas no influence of the substratum hydrophobicity on the inhibition of E. faecalis adhesion was noticed for experiments performed in buffer. The biosurfactant surlactin, as released by several Lactobacillus isolates, might open the way to the development of antiadhesive biologic coatings for catheter materials. It should be considered, however, that these results are preliminary and that the efficiency of the biosurfactant is probably affected not only by the hydrophobicity of the substratum and the suspending fluid, but also by the type of uropathogen involved.


[Erectile dysfunction and quality of life in patients with chronic renal failure].
Erectile dysfunction (ED) is associated with a reduced quality of life; it represents a risk factor for the development of depression. ED may induce depression, loss of self-esteem, poor self-image, anxiety, and tension in the relationship with the partner. These emotional disturbances can create physical conditions that lead to increased difficulty in achieving an erection. Depression can deprive a person of the ability to experience many of life's pleasures. It not only affects the mind but also the body--often in unexpected ways. As a result, many men who have been diagnosed with depression find themselves suffering from another condition: ED. Sexual dysfunction is a big problem also in patients with chronic renal failure and seriously affects their quality of life. About 40% of men on dialysis suffer from ED. Many uremic patients have additional symptoms including reduction of libido and a decreased frequency of sexual intercourse. With the start of dialysis some of these symptoms may improve, without, however, returning to normal.


Color processing in macaque striate cortex: relationships to ocular dominance, cytochrome oxidase, and orientation.
We located clusters of color-selective neurons in macaque striate cortex, as mapped with optical imaging and confirmed with electrophysiological recordings. By comparing responses to an equiluminant red/green stimulus versus a high-contrast luminance stimulus, we were able to reveal a patchy distribution of color selectivity. Other color imaging protocols, when compared with electrophysiological data, did not reliably indicate the location of functional structures. The imaged color patches were compared with other known functional subdivisions of striate cortex. There was a high degree of overlap of the color patches with the cytochrome-oxidase (CO) blobs. The patches were often larger than a single blob in size, however, and in some instances spanned two neighboring blobs. More than one-half (56%) of the color-selective patches seen in optical imaging were not confined to one ocular dominance (OD) column. Almost one-quarter of color patches (23%) extended across OD columns to encompass two blobs of different eye preference. We also compared optical images of orientation selectivity to maps of color selectivity. Results indicate that the layout of orientation and color selectivity are not directly related. Specifically, despite having similar scales and distributions, the maps of orientation and color selectivity were not in consistent alignment or registration. Further, we find that the maps of color selectivity and of orientation are each only loosely related to maps of OD. This description stands in contrast to a common depiction of color-selective regions as identical to CO blobs, appearing as pegs in the centers of OD columns in the classical "ice cube" model. These results concerning the pattern of color selectivity in V1 support the view (put forth in previous imaging studies of the organization of orientation and ocular dominance) that there is not a fundamental registration of functional hypercolumns in V1.


Serum immunoglobulins, rheumatoid factor, and pneumoconiosis in coal miners with rheumatoid arthritis.
The occurrence and severity of pneumoconiosis were studied in 100 coal miners with rheumatoid arthritis (RA) and compared to findings in a geographically relevant survey of coal workers' pneumoconiosis. Contrary to European reports, miners with RA were not found to have an excessive frequency or severity of pneumoconiosis. In 55 of these men, serum immunoglobulin levels and rheumatoid factor were compared with data from matched RA patients with no history of silica exposure. The immunochemical results were unrelated to the stage of pneumoconiosis, nor did they differ from those in the control group.


Validation of a multiplex reverse transcription and pre-amplification method using TaqMan(®) MicroRNA assays.
Since the discovery of microRNAs (miRNAs), different approaches have been developed to label, amplify and quantify miRNAs. The TaqMan(®) technology, provided by Applied Biosystems (ABIs), uses a stem-loop reverse transcription primer system to reverse transcribe the RNA and amplify the cDNA. This method is widely used to identify global differences between the expression of 100s of miRNAs across comparative samples. This technique also allows the quantification of the expression of targeted miRNAs to validate observations determined by whole-genome screening or to analyze few specific miRNAs on a large number of samples. Here, we describe the validation of a method published by ABIs on their web site allowing to reverse transcribe and pre-amplify multiple miRNAs and snoRNAs simultaneously. The validation of this protocol was performed on human muscle and plasma samples. Fast and cost efficient, this method achieves an easy and convenient way to screen a relatively large number of miRNAs in parallel.


Radiolabeled peptides: current and new perspectives.
Radiolabeled peptides have been the subject of research for over 20 years and during that time possibility/variety of peptide receptor imaging and later targeted radiotherapy increased significantly. The targeted receptors belong to the large family of G-protein-coupled receptors or tyrosine kinases receptors partially connected with them. They both regulate large signaling networks, control multiple cell functions and are implicated in many diseases including cancers. The essential feature of peptides used in nuclear medicine involves their ability to binding with high affinity and specify to their receptors overexpressed on tumor cells. Currently most important peptide radiotracers are somatostatin, GLP-1, bombesin, gastrin/cholecystokinin-2, neurokinin type 1, CXCR4, EGF, VEGF and integrins. These tracers are mainly based on nuclides which are radiometals or on 18F and may be used in both SPECT or PET techniques as well as for hybrid imaging. Using of chelators suitable for peptide labeling with diagnostic and therapeutic radionuclids enables the theranostic approach. In this review we will provide a brief overview over currently available radiopharmaceuticals based on different groups of peptides.


All That Glitters Is Not Gold" - A Case of an Occult Foreign Body in the Lung with Elevated 2-[18F]-Fluoro-2-deoxy-D-glucose (FDG) Uptake Mimicking Bronchogenic Carcinoma.
Combined positron emission tomography/computed tomography (PET/CT) using the glucose analogue 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) has become the standard of care in oncological patients. However, due to the non-specific nature of FDG uptake, there are many physiological variants and benign pathological entities that also demonstrate augmented glucose metabolism, such as inflammatory and infective processes. Undiagnosed and retained foreign bodies (occult foreign bodies) in the lung can induce inflammatory reaction consisting of polymorphonuclear neutrophils, macrophages, and granulation tissue resulting in intense FDG uptake because of high metabolic activity and cell turnover. Here, we present a case of an occult foreign body imitating a tumor on PET/CT.


Interaction Between Methicillin-Resistant Staphylococcus aureus (MRSA) and Acanthamoeba polyphaga.
The interactions that occur between bacteria and amoebae can give through mutual relations, where both organisms benefit from the association or parasitic in which one organism benefits at the expense of the other. When these organisms share the same environment, it can result in some changes in the growth of organisms, in adaptation patterns, in morphology, development or even in their ability to synthesize proteins and other substances. In this study, the interaction between Acanthamoeba polyphaga and Staphylococcus aureus (MRSA) was evaluated using a co-culture model at different incubation times. The results showed that 89% of amoebic cells remained viable after contact with the bacteria. The bacterial isolate was visualized inside the amoeba through confocal microscopy and fluorescence for up to 216 h of co-cultivation. The lysate of amoebic culture increased the growth of S. aureus (MRSA), and the effect of supernatant of culture inhibited bacterial growth over the incubation times, suggesting that A. polyphaga produced some metabolite, that inhibited the growth of bacteria. Moreover, the encystment of the A. polyphaga was increased by the bacteria presence. The results show that A. polyphaga and S. aureus interaction may have an important influence on survival of both, and specially indicate a possible effect on the metabolics characteristics each other.


Photoinduced organic field-effect transistor based on poly-3-hexyl-thiophene active layer.
Top-contact organic field-effect transistors (OFETs) were fabricated by using a poly-3-hexyl-thiophene (P3HT) active layer. The characteristics of OFETs without and with the light-illumination were investigated. The experimental results indicate that the light has a great influence on the OFETs properties. After the light-illumination, the drain current and carrier mobility were increased, the threshold was decreased, and the on/off ratio was enhanced.


Establishment of a system for screening autophagic flux regulators using a modified fluorescent reporter and CRISPR/Cas9.
Autophagy is a mechanism of bulk protein degradation that plays an important role in regulating homeostasis in many organisms. Among several methods for evaluating its activity, a fluorescent reporter GFP-LC3-RFP-LC3ΔG, in which GFP-LC3 is cleaved by ATG4 following autophagic induction and degraded in lysosome, has been used for monitoring autophagic flux, which is the amount of lysosomal protein degradation. In this study, we modified this reporter by exchanging GFP for pHluorin, which is more sensitive to low pH, and RFP to mCherry, to construct pHluorin-LC3-mCherry reporter. Following starvation or mTOR inhibition, the increase of autophagic flux was detected by a decrease of the fluorescent ratio of pHluorin to mCherry; our reporter was also more sensitive to autophagy-inducing stimuli than the previous one. To establish monitoring cells for mouse genome-wide screening of regulators of autophagic flux based on CRISPR/Cas9 system, after evaluating knockout efficiency of clones of Cas9-expressing MEFs, we co-expressed our reporter and confirmed that autophagic flux was impaired in gRNA-mediated knockout of canonical autophagy genes. Finally, we performed genome-wide gRNA screening for genes inhibiting starvation-mediated autophagic flux and identified previously reported genes such as Atgs. Thus, we have successfully established a system for screening of genes regulating autophagic flux with our pHluorin-LC3-mCherry reporter in mice.


Paenibacillus aceti sp. nov., isolated from the traditional solid-state acetic acid fermentation culture of Chinese cereal vinegar.
A Gram-stain-negative, rod-shaped, motile, endospore-forming, facultatively anaerobic bacterium, designated strain L14T, was isolated from the traditional acetic acid fermentation culture of Chinese cereal vinegars. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain L14T was affiliated to the genus Paenibacillus, most closely related to Paenibacillus motobuensis MC10T with 97.8 % similarity. Chemotaxonomic characterization supported the allocation of the strain to the genus Paenibacillus. The polar lipid profile of strain L14T contained the major compounds diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The predominant menaquinone was MK-7, and the major fatty acid components were anteiso-C15 : 0, iso-C15 : 0 and C16 : 0. The DNA G+C content of strain L14T was 49.9 mol%. The DNA-DNA relatedness value between strain L14T and P. motobuensis MC10T was 51.2 %. The results of physiological and biochemical tests allowed phenotypic differentiation of strain L14T from closely related species. On the basis of phenotypic and chemotaxonomic analyses, phylogenetic analysis and DNA-DNA relatedness values, strain L14T is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus aceti sp. nov. is proposed. The type strain is L14T (=CGMCC 1.15420T=JCM 31170T).


Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR.
HIV seronegative individuals with high-risk behavior were tested for HIV infection by sensitive virus isolation techniques using T4 lymphocytes and monocyte/macrophages, and by detection of proviral DNA using PCR with three different sets of nested primers. No evidence of HIV infection was found among the 31 seronegative high-risk subjects, either by virus isolation of by PCR (97.5% confidence limits, 0-11). Our results indicate that ongoing HIV infection in seronegative persons at high risk of infection is a rare event.


Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems.
Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acid<cimetidine<atenolol<amitriptyline<diltiazem. Comparison of the experimental observations with predictions from an existing model for estimating sorption revealed the model worked poorly for the study pharmaceuticals. Multiple linear regression analysis was therefore used to develop new models for estimating sorption of individual pharmaceuticals based on sediment properties. The analyses indicated that sorption is related to properties such as Log Dow of a compound in the sediment (lipophilicity corrected for the sediment pH), cation exchange capacity, clay%, organic carbon content and exchangeable Ca(2+), although, with the exception of atenolol, robust relationships between sediment properties and sorption were not obtained. Overall, the results demonstrate how complex the processes are that drive the sorption of pharmaceuticals in sediments and highlight the need for generation of further experimental data and further model development work.


Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-β.
Alveolar epithelial cell (AEC) injury and apoptosis are prominent pathological features of idiopathic pulmonary fibrosis (IPF). There is evidence of AEC plasticity in lung injury repair response and in IPF. In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to transforming growth factor-β1 (TGF-β1). Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expressions of mesenchymal markers, phenotype, and function were analyzed. Pharmacological protein kinase inhibitors were utilized to screen for SMAD-dependent and -independent pathways. SMAD and FAK signaling was analyzed using siRNA knockdown, inhibitors, and expression of a mutant construct of FAK. Apoptosis was measured using cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. TGF-β1 induced the acquisition of mesenchymal markers, including α-smooth muscle actin, in RLE-6TN cells and enhanced the contraction of three-dimensional collagen gels. This phenotypical transition or plasticity, epithelial-myofibroblast plasticity (EMP), is dependent on SMAD3 and FAK signaling. FAK activation was found to be dependent on ALK5/SMAD3 signaling. We observed that TGF-β1 induces both EMP and apoptosis in the same cell culture system but not in the same cell. While blockade of SMAD signaling inhibited EMP, it had a minimal effect on apoptosis; in contrast, inhibition of FAK signaling markedly shifted to an apoptotic fate. The data support that FAK activation determines whether AECs undergo EMP vs. apoptosis in response to TGF-β1 stimulation. TGF-β1-induced EMP is FAK- dependent, whereas TGF-β1-induced apoptosis is favored when FAK signaling is inhibited.


In Vivo Delivery of CRISPR/Cas9 for Therapeutic Gene Editing: Progress and Challenges.
The successful use of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based gene editing for therapeutics requires efficient in vivo delivery of the CRISPR components. There are, however, major challenges on the delivery front. In this Topical Review, we will highlight recent developments in CRISPR delivery, and we will present hurdles that still need to be overcome to achieve effective in vivo editing.


Grandparentage assignments identify unexpected adfluvial life history tactic contributing offspring to a reintroduced population.
Diversity in life history tactics contributes to the persistence of a population because it helps to protect against stochastic environments by varying individuals in space and time. However, some life history tactics may not be accounted for when assessing the demographic viability of a population. One important factor in demographic viability assessments is cohort replacement rate (CRR), which is defined as the number of future adults produced by an adult. We assessed if precocial resident males (<age-3) and adfluvial Chinook salmon (Oncorhynchus tshawytscha), adults that reside in freshwater their entire lives, contributed offspring to a reintroduced population from 2008 to 2013. We found that 9 ± 5% of offspring with an unassigned parent remained unexplained after accounting for sources of human error. Using grandparentage assignments, we identified 31 precocial resident males and 48 probable adfluvial Chinook salmon produced by anadromous mate pairs from 2007 to 2012. Previously published CRR estimates for the 2007 and 2008 reintroduced adults, based on only anadromous returning adult offspring, were 0.40 and 0.31, respectively. By incorporating adfluvial females, we found CRR estimates increased by 17% (CRR: 0.46) and 13% (CRR: 0.35) for the 2007 and 2008 cohorts, respectively.


Silicon optical filters reconfigured from a 16 × 16 Benes switch matrix.
Reconfigurable optical filters with tailorable performances are highly demanded in multi-purpose adaptive signal processing applications. We demonstrate infinite impulse response (IIR) silicon optical filters with a variable filter order by switching the optical path in a 16 × 16 Benes switch chip. The basic unit of the optical filter is a dual-ring assisted Mach-Zehnder interferometer. TiN microheaters are integrated in both ring resonators for resonance control, allowing for continuous tuning of the filter center wavelength and the bandwidth. Multiple high-order optical filters from the 2nd order up to the 14th order are obtained. The filter bandwidth tuning range is from 0.19 nm (23.75 GHz) to 1.06 nm (132.5 GHz) with a 1-dB in-band ripple. The out-of-band rejection ratio exceeds 30 dB for the 8th and 10th-order filters, limited by the inter-path optical crosstalk in the Benes architecture. The results point to new ways of reutilizing an existing switch matrix to flexibly construct wavelength-filtering devices.


Mycobacterial RNA polymerase forms unstable open promoter complexes that are stabilized by CarD.
Escherichia coli has served as the archetypal organism on which the overwhelming majority of biochemical characterizations of bacterial RNA polymerase (RNAP) have been focused; the properties of E. coli RNAP have been accepted as generally representative for all bacterial RNAPs. Here, we directly compare the initiation properties of a mycobacterial transcription system with E. coli RNAP on two different promoters. The detailed characterizations include abortive transcription assays, RNAP/promoter complex stability assays and DNAse I and KMnO4 footprinting. Based on footprinting, we find that promoter complexes formed by E. coli and mycobacterial RNAPs use very similar protein/DNA interactions and generate the same transcription bubbles. However, we find that the open promoter complexes formed by E. coli RNAP on the two promoters tested are highly stable and essentially irreversible (with lifetimes much greater than 1 h), while the open promoter complexes on the same two promoters formed by mycobacterial RNAP are very unstable (lifetimes of about 2 min or less) and readily reversible. We show here that CarD, an essential mycobacterial transcription activator that is not found in E. coli, stabilizes the mycobacterial RNAP/open promoter complexes considerably by preventing transcription bubble collapse.


An 8-month history of meningitis in an extremely low birth weight infant? - Long-lasting Infection with Ureaplasma parvum.
Ureaplasma spp. have been implicated in the pathogenesis of both preterm labor and neonatal morbidity including pneumonia and sepsis and the development of chronic lung disease of prematurity. Data on Ureaplasma meningitis are limited and partly controversially discussed. We report the unique case of a 9-month-old infant with progressive internal hydrocephalus of unknown origin and developmental delay due to a history of>200 days of inflammation of the central nervous system. The female extremely low birth weight infant had been referred to our hospital for ventriculoperitoneal shunt implantation. She had been born at 26+3 weeks of gestation with a birth weight of 940 g. With the exception of a moderate respiratory distress syndrome, postnatal period had been reported uneventful. However, internal hydrocephalus had become manifest at 4 weeks of postnatal age. Intraventricular hemorrhage had not been documented by cranial ultrasound and magnetic resonance imaging. Cerebrospinal fluid (CSF) analysis had repetitively revealed pronounced inflammation reflected by pleocytosis (50-86 leukocytes/μL, 60% lymphocytes), CSF protein levels of 578-1,026 mg/dL and undetectable CSF glucose. Although suggesting bacterial meningitis, microbial diagnostics had not been indicative, and empirical antibiotics had not affected the CSF findings. On admission to our hospital, CSF analysis still documented significant inflammation (125 leukocytes/μL, CSF protein 565 mg/dL, CSF glucose<2 mg/dL). Due to a prenatal history of cerclage, we initiated microbial diagnostics on Ureaplasma spp. and Mycoplasma hominis. U. parvum was detected in CSF by culture and PCR, no other pathogens were isolated. On intravenous treatment with chloramphenicol, CSF profile continuously normalized, and cultures and PCR became negative. Treatment was continued for 3 weeks, and the infant was discharged after uncomplicated ventriculoperitoneal shunt placement. During a 12-month observation period she has shown encouraging recovery. In preterm infants, in particular, internal hydrocephalus of unknown origin and sustained CSF inflammation are highly suggestive of Ureaplasma meningitis. Our case highlights that infection may escape detection if not explicitly considered, since microbial diagnosis requires complex media and PCR.


An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions.
This study provides the first characterization of early developmental trajectories of corpus callosum (CC) segments in rhesus macaques using noninvasive MRI techniques and assesses long-term effects of neonatal amygdala or hippocampal lesions on CC morphometry. In Experiment 1, 10 monkeys (5 males) were scanned at 1 week-2 years of age; eight additional infants (4 males) were scanned once at 1-4 weeks of age. The first 8 months showed marked growth across all segments, with sustained, albeit slower, growth through 24 months. Males and females had comparable patterns of CC maturation overall, but exhibited slight differences in the anterior and posterior segments, with greater increases in the isthmus for males and greater increases in the rostrum for females. The developmental changes are likely a consequence of varying degrees of axonal myelination, redirection, and pruning. In Experiment 2, animals with neonatal lesions of the amygdala (n = 6; 3 males) or hippocampus (n = 6; 4 males) were scanned at 1.5 years post-surgery and compared to scans of six control animals from Experiment 1. Whereas amygdala damage yielded larger rostral and posterior body segments, hippocampal damage yielded larger rostrum and isthmus. These differences demonstrate that early perturbations to one medial temporal lobe structure may produce extensive and long-lasting repercussions in other brain areas. The current findings emphasize the complexity of neural circuitry putatively subserving neurodevelopmental disorders such as autism spectrum disorder and Williams syndrome, which are each characterized by malformations and dysfunction of complex neural networks that include regions of the medial temporal lobe.


D. Campbell Meyers, M.D., L.R.C.P., M.R.C.S. (Eng.) 1863-1927, pioneer of Canadian general hospital psychiatry.
The paper describes the pioneering contributions of Dr. D. Campbell Meyers (1863--1927) to general hospital psychiatry during the first decade of this century at the Toronto General Hospital where, between 1906 - 1911, he operated the first public general hospital psychiatric unit in Canada. His conflict with Dr. C. K. Clarke who opposed his efforts is documented. To honour Meyers' contributions the Department of Psychiatry, Toronto General Hospital, has been named "The D. Campbell Meyers Memorial Department of Psychiatry".


Meconium: a marker for peripartum infection.
To test the hypothesis that the presence of meconium-stained amniotic fluid (AF) is associated with maternal and neonatal infection, both before and after delivery. Nine hundred thirty-six laboring women were analyzed for the presence of meconium in amniotic fluid and occurrence of peripartum infection. Meconium was assessed clinically as thin, moderate, or thick. Intra-amniotic infection and endometritis were diagnosed by standard definitions. All patients were tested for vaginal group B streptococcus, bacterial vaginosis, and other aerobic organisms. Meconium-stained AF was present in 28% of the study participants (9% thin, 12% moderate, 7% thick). The presence of meconium was associated with increased intra-amniotic fluid (17% versus 9%, relative risk [RRI 1.98, 95% confidence interval [CI] 1.3, 3.1), endometritis (10% versus 5%, RR 2.38, 95% CI 1.3, 4.4), and total infection (25% versus 13%, RR 2.19, 95% CI 1.5, 3.2). Thick meconium had higher infection rates than clear AF (44% versus 13%, RR 5.18, 95% CI 2.9, 9.3). Meconium was associated independently with peripartum infection by multiple logistic regression (RR 1.28, 95% CI 1.1, 1.6). Meconium-stained AF is associated with increased peripartum infection, independent of other risk factors for infection. Thick meconium, in particular, is associated with a marked increase in peripartum infectious morbidity.


Suspected anaphylactic reaction associated with sugammadex: a case report.
We describe a case of a 35-year-old male patient who was scheduled for laparoscopic cholecystectomy and developed a life-threatening anaphylactic reaction 2 min after the administration of sugammadex. He manifested erythematous wheals on the entire body, dyspnea, hypotension, and tachycardia. These symptoms disappeared after the administration of epinephrine. The patient recovered and was discharged at postoperative day 5 without any complications. After 7 weeks, we performed a skin prick test, and there was a weakly positive reaction for sugammadex. This case is suspected anaphylaxis associated with sugammadex, and we need to be aware that the use of sugammadex is associated with a serious risk of anaphylaxis.


Relationship between activation and apoptosis in platelets.
Phosphatidylserine (PS) externalization is a marker for the nucleated cell apoptosis, and refers cellular activation rather than apoptosis in platelets. On the other hand, several similarities exist between platelet activation and apoptosis in nucleated cells. Herewith we investigated the relationship between platelet activation and platelet apoptosis. Platelets isolated from fresh blood of 22 healthy volunteers were incubated with and without calcium ionophore A23187. Platelet activation was evaluated with CD62P and CD63 antibodies, whereas apoptosis with intracellular anti caspase 3-antibody and JC-1 cationic dye. In order to detect PS externalization we used Annexin V by flow cytometry at the beginning, 20th min and 5th hours of the incubation, respectively. There were positive correlations between caspase-3 activation and PS externaization, ∆Ψm depolarization, CD63, and also between PS externaization and CD62P in incubations with A23187 at 5th hours of incubations. These results suggest that there is a relationship between activation and apoptosis in platelets, and platelet activation may progress to platelet apoptosis.


Propagation of fatigue cracks in acrylic bone cements containing different radiopaque agents.
In this work three iodine-containing monomers were proposed as new radiopaque agents for acrylic bone cements. In previous studies the addition of iodine-containing methacrylate monomers provided a statistically significant increase in tensile stress, fracture toughness and ductility, with respect to the barium sulphate (BaSO4)-containing cement. However, since fatigue resistance is one of the main properties required to ensure a good long-term performance of permanent prostheses, it is important to compare the fatigue properties of these new bone cement formulations with the radiolucent and BaSO4-containing bone cements. Because the acrylic cements have initial cracks, fatigue crack propagation studies were performed. It can be observed that these acrylic cements followed the Paris-Erdogan model. The results showed that the addition of some organic radiopacifiers (DISMA, TIBMA) increased the fatigue crack propagation resistance as compared to the radiolucent cement, being similar to the BaSO4-containing cement. The radiolucent cement showed a low crack propagation resistance.


The Cancer Imaging Archive (TCIA): maintaining and operating a public information repository.
The National Institutes of Health have placed significant emphasis on sharing of research data to support secondary research. Investigators have been encouraged to publish their clinical and imaging data as part of fulfilling their grant obligations. Realizing it was not sufficient to merely ask investigators to publish their collection of imaging and clinical data, the National Cancer Institute (NCI) created the open source National Biomedical Image Archive software package as a mechanism for centralized hosting of cancer related imaging. NCI has contracted with Washington University in Saint Louis to create The Cancer Imaging Archive (TCIA)-an open-source, open-access information resource to support research, development, and educational initiatives utilizing advanced medical imaging of cancer. In its first year of operation, TCIA accumulated 23 collections (3.3 million images). Operating and maintaining a high-availability image archive is a complex challenge involving varied archive-specific resources and driven by the needs of both image submitters and image consumers. Quality archives of any type (traditional library, PubMed, refereed journals) require management and customer service. This paper describes the management tasks and user support model for TCIA.


A holistic picture of Austronesian migrations revealed by phylogeography of Pacific paper mulberry.
The peopling of Remote Oceanic islands by Austronesian speakers is a fascinating and yet contentious part of human prehistory. Linguistic, archaeological, and genetic studies have shown the complex nature of the process in which different components that helped to shape Lapita culture in Near Oceania each have their own unique history. Important evidence points to Taiwan as an Austronesian ancestral homeland with a more distant origin in South China, whereas alternative models favor South China to North Vietnam or a Southeast Asian origin. We test these propositions by studying phylogeography of paper mulberry, a common East Asian tree species introduced and clonally propagated since prehistoric times across the Pacific for making barkcloth, a practical and symbolic component of Austronesian cultures. Using the hypervariable chloroplast ndhF-rpl32 sequences of 604 samples collected from East Asia, Southeast Asia, and Oceanic islands (including 19 historical herbarium specimens from Near and Remote Oceania), 48 haplotypes are detected and haplotype cp-17 is predominant in both Near and Remote Oceania. Because cp-17 has an unambiguous Taiwanese origin and cp-17-carrying Oceanic paper mulberries are clonally propagated, our data concur with expectations of Taiwan as the Austronesian homeland, providing circumstantial support for the "out of Taiwan" hypothesis. Our data also provide insights into the dispersal of paper mulberry from South China "into North Taiwan," the "out of South China-Indochina" expansion to New Guinea, and the geographic origins of post-European introductions of paper mulberry into Oceania.


Method of computed tomography-based stereotactic biopsy with arteriographic control.
A method for computed tomography (CT)-based stereotactic biopsy of intracranial neoplasms with arteriographic control is described. Stereotactic CT and digitized stereotactic arteriographic data are input to a three-dimensional computer matrix that corresponds to the coordinate system of a stereotactic frame located in the operating room. A site for biopsy is selected by cursor from the CT display screen. The computer calculates and outputs the mechanical adjustments of the stereotactic frame necessary to place the target point into the focal point of the frame. Horizontal and vertical approach angles are determined from the digitized arteriogram and are displayed as settings on the stereotactic frame that represent an avascular trajectory along which the lesion may be biopsied safely. This procedure has been used successfully in 86 patients, with no morbidity or mortality.


Confirmative biophilic framework for heritage management.
Heritage managers often reuse heritage sites to attract tourists and conserve the sites. Not all adaptive heritage reuses achieve sustainable development. Biophilia is an innate, biological tendency to be close to natural and cultural elements, which may be a critical motivation for achieving sustainable heritage management. Past studies used qualitative and quantitative methods to extract participants' pull and push motivations toward heritage tourism and captured the six motivations of the biophilia framework that should be confirmed: heritage architecture; art activity; wide nature; regional attraction; recreational benefits; and long-term values. The purpose of this study was to conduct a confirmatory factor analysis to test the biophilia framework for understanding biophilic heritage tourism. A questionnaire with 18 items of heritage tourism motivation was used to explore the purpose of this study. A total of 193 valid questionnaires were obtained. Confirmatory factor analysis was used to examine the six motivations of the biophilia framework. The results indicated that heritage tourism motivation consisted of a second-order six-factor structure with high validity and reliability. These six dimensions reflected the biophilic requirements and provided a biophilic planning principle to achieve sustainable heritage management to satisfy the needs of the participants.


Dopamine levels of two classes of vesicles are differentially depleted by amphetamine.
Differential depletion of neurotransmitter by amphetamine in two classes of vesicles, termed large vesicles and small vesicles, has been studied with amperometry. Carbon fiber microelectrodes have been used to monitor and quantify exocytotic events. Current transients, corresponding to individual exocytotic events, have been obtained from the cell body of the dopamine-containing neuron of Planorbis corneus. The dopamine released from individual vesicles of these cells has been compared for cells treated with D-amphetamine vs. control cells. Our results show that amphetamine has differential effects on the release of dopamine from the two classes of vesicles. Thus, it is concluded that at low concentrations, amphetamine preferentially depletes the large vesicles with a minimal effect on the small vesicles. At high concentrations, amphetamine depletes small vesicles more strongly than large vesicles although amphetamine continues to deplete the large vesicles in a dose-dependent manner. Our data appear to indicate that the two classes of vesicles observed in the Planorbis dopamine neuron might have different mechanisms associated with transmitter depletion.


Nail molybdenum and zinc contents in populations with low and moderate incidence of esophageal cancer.
The objective of our study was to compare the zinc and molybdenum contents of nails in two populations at high and low risk for esophageal cancer in northern Iran. Four groups were studied including a control group in Tehran--a low-risk area (n=20); a group of patients with esophageal cancer from Sari--a moderate- risk region in northern Iran (n=20); a group of patients' family members (n=20); and a control group in Sari (n=40). Molybdenum and zinc levels were measured in their nail samples using flame atomic absorption spectrometry. Both molybdenum and Zinc were significantly (P<0.01) lower in the Sari control group (molybdenum: 0.472 ppm, zinc: 173.0 ppm) compared with the Tehran control group (molybdenum: 0.740 ppm, zinc: 251.5 ppm). These elements were lower in content in patients with esophageal cancer (molybdenum: 0.283 ppm, zinc: 126.5 ppm) compared with the Sari control group (P<0.05 for molybdenum and P<0.001 for zinc). Only zinc was significantly (P<0.001) lower in patients compared with their family members (molybdenum: 0.456 ppm, zinc: 175.5 ppm). No differences were found between the Sari control group and the patients' family members in any of the two elements. Zinc and molybdenum levels are much lower in north of Iran--a moderate- risk area for esophageal cancer--compared with Tehran--a low-risk area. Based on these results, more investigations on the relations of trace elements with esophageal cancer in high-risk areas in northern Iran are warranted.


An Omnidirectional Vision Sensor Based on a Spherical Mirror Catadioptric System.
The combination of mirrors and lenses, which defines a catadioptric sensor, is widely used in the computer vision field. The definition of a catadioptric sensors is based on three main features: hardware setup, projection modelling and calibration process. In this paper, a complete description of these aspects is given for an omnidirectional sensor based on a spherical mirror. The projection model of a catadioptric system can be described by the forward projection task (FP, from 3D scene point to 2D pixel coordinates) and backward projection task (BP, from 2D coordinates to 3D direction of the incident light). The forward projection of non-central catadioptric vision systems, typically obtained by using curved mirrors, is usually modelled by using a central approximation and/or by adopting iterative approaches. In this paper, an analytical closed-form solution to compute both forward and backward projection for a non-central catadioptric system with a spherical mirror is presented. In particular, the forward projection is reduced to a 4th order polynomial by determining the reflection point on the mirror surface through the intersection between a sphere and an ellipse. A matrix format of the implemented models, suitable for fast point clouds handling, is also described. A robust calibration procedure is also proposed and applied to calibrate a catadioptric sensor by determining the mirror radius and center with respect to the camera.


A two-phase gradual silver release mechanism from a nanostructured TiAlV surface as a possible antibacterial modification in implants.
Titanium biomaterials are widely used in the medical field due to their biocompatibility and excellent corrosion and mechanical resistance. However, these materials have no antibacterial properties. To obtain an antibacterial active surface, a nanostructure of Ti6Al4V alloy was created. This specific nanostructure contained nanotubes and micro-cavities and was used as a substrate for silver anchoring. The electrochemical approach to silver reduction was studied. It is a common approach for silver deposition and in this work, inhomogeneities in the nanostructure were used as a preferential area for silver localisation. The galvanostatic regimen of deposition allowed for a technically quantitative process and the required silver placement. The experimental conditions used enabled testing and silver dissolution rate evaluation within a reasonable time span. Based on the corrosion and analytical results (EDS, XPS and ICP-MS), a two-phase silver release mechanism was confirmed. The openings of the individual nanotubes were filled with silver nanoparticles, whose release was relatively fast. By contrast, the silver anchored inside the cavities allowed the silver to release gradually. Antibacterial efficiency against Staphylococcus aureus and Escherichia coli was successfully demonstrated. Cytotoxicity testing with murine fibroblasts showed cell metabolic activity far above the normative limit of 70%.


An evaluation of continuous positive airway pressure (CPAP) therapy in the treatment of hypernasality following traumatic brain injury: a report of 3 cases.
To evaluate the effectiveness of continuous positive airway pressure (CPAP) therapy in the treatment of hypernasality following traumatic brain injury (TBI). An A-B-A experimental research design. Assessments were conducted prior to commencement of the program, midway, immediately posttreatment, and 1 month after completion of the CPAP therapy program. Three adults with dysarthria and moderate to severe hypernasality subsequent to TBI. Perceptual evaluation using the Frenchay Dysarthria Assessment, the Assessment of Intelligibility of Dysarthric Speech, and a speech sample analysis, and instrumental evaluation using the Nasometer. Between assessment periods, varying degrees of improvement in hypernasality and sentence intelligibility were noted. At the 1-month post-CPAP assessment, all 3 participants demonstrated reduced nasalance values, and 2 exhibited increased sentence intelligibility. CPAP may be a valuable treatment of impaired velopharyngeal function in the TBI population.


Biodegradable Smart Nanogels: A New Platform for Targeting Drug Delivery and Biomedical Diagnostics.
Nanogels (or nanohydrogels) have been extensively investigated as one of the most promising nanoparticulate biomedical platforms owing to their advantageous properties that combine the characteristics of hydrogel systems with nanoparticles. Among them, smart nanogels that have the ability to respond to external stimuli, such as pH, redox, temperature, enzymes, light, magnetic field and so forth, are most attractive in the area of drug delivery. Besides, numerous multifunctionalized nanogels with high sensitivity and specificity were designed for diagnostic applications. In this feature article, we have reviewed and discussed the recent progress of biodegradable nanogels as smart nanocarriers of anticancer drugs and biomedical diagnostic agents for cancer.


Medial temporal lobe damage causes deficits in episodic memory and episodic future thinking not attributable to deficits in narrative construction.
The medial temporal lobe (MTL) makes critical contributions to episodic memory, but its contributions to episodic future thinking remain a matter of debate. By one view, imagining future events relies on MTL mechanisms that also support memory for past events. Alternatively, it has recently been suggested that future thinking is independent of MTL-mediated processes and can be supported by regions outside the MTL. The current study investigated the nature and necessity of MTL involvement in imagining the future and tested the novel hypothesis that the MTL contributes to future thinking by supporting online binding processes related to narrative construction. Human amnesic patients with well characterized MTL damage and healthy controls constructed narratives about (1) future events, (2) past events, and (3) visually presented pictures. While all three tasks place similar demands on narrative construction, only the past and future conditions require memory/future thinking to mentally generate relevant narrative information. Patients produced impoverished descriptions of both past and future events but were unimpaired at producing detailed picture narratives. In addition, future-thinking performance positively correlated with episodic memory performance but did not correlate with picture narrative performance. Finally, future-thinking impairments were present when MTL lesions were restricted to the hippocampus and did not depend on the presence of neural damage outside the MTL. These results indicate that the ability to generate and maintain a detailed narrative is preserved in amnesia and suggest that a common MTL mechanism supports both episodic memory and episodic future thinking.


A hierarchy of disulfide-bonded subunits: the quaternary structure of Eudistylia chlorocruorin.
The quaternary structure of the cysteine-rich, approximately 3500-kDa chlorocruorin (Chl) from the marine polychaete Eudistylia vancouverii was investigated using maximum entropy deconvolution of the electrospray ionization mass spectra (ESIMS). The native Chl provided two groups of peaks, at approximately 25 and approximately 33 kDa, and one peak at approximately 66 kDa. ESIMS of the reduced and reduced and carbamidomethylated Chl and of its subunits obtained by HPLC provided the complete subunit composition of the Chl. Two groups of nonglobin linker chains were observed: L1a-f (25 000.4, 25 017.9, 25 039.6, 25 057.0, 25 074.4 and 25 096.8 Da) and L2a-d (25 402.7, 25 446.0, 25 461.6 and 25 478.3Da) (+/-2.5 Da), with relative intensities L1:L2 = 5:2. Six globin chains were found, a1, a2, and b1-4, with reduced masses of 16 051.5, 16 172.4, 16 853.5, 17 088.9, 17 161.2 and 17 103.6 (+/-1.0 Da) and relative intensities of 8:4:1:4:2:1, respectively. Disulfide-bonded dimers and a tetramer of globin chains were identified: D1 = a1 + b3 at 33 207.1; D2 at 33 374.1, which had a cysteinylated Cys (a2 + b2 + Cys); and D3 = a1 + b4 at 33 149.4 Da (+/-3.0 Da), with relative intensities D1:D2:D3 = 5:4:1 and T = a1 + a2 + b1 + b2 at 66 154.8 +/- 4.0 Da. A 206-kDa dodecamer subunit obtained by dissociation of the Chl in 4 M urea [Qabar, A. N., et al. (1991) J. Mol. Biol. 222, 1109-1129], was found to consist only of tetramers T. A model was proposed for the Chl, based on a dimer:tetramer ratio of 2:1: four 206-kDa dodecamers (trimer of tetramers) and 48 dimers tethered to a framework of 30 L1 and 12 L2 linker chains. The 144 globin chains (2480 kDa) and 42 linker chains (1059 kDa) provide a total mass of 3539 kDa, in good agreement with the 3480 +/- 225 kDa determined previously by STEM mass mapping. The hierarchy of disulfide-bonded globin subunits observed for Eudistylia Chl provides a built-in heterogeneity of hexagonal bilayer structures.


Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature.
Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.


Mnemonic scaffolds vary in effectiveness for serial recall.
Memory champions remember vast amounts of information in order and at first encounter by associating each study item to an anchor within a scaffold - a pre-learned, structured memory. The scaffold provides direct-access retrieval cues. Dominated by the familiar-route scaffold (Method of Loci), researchers have little insight into what characteristics of scaffolds make them effective, nor whether individual differences might play a role. We compared participant-generated mnemonic scaffolds: (a) familiar routes (Loci), (b) autobiographical stories (Story), (c) parts of the human body (Body), and (d) routine activities (Routine Activity). Loci, Body, and Story Scaffolds benefited serial recall over Control (no scaffold). The Body and Loci Scaffold were equally superior to the other scaffolds. Measures of visual imagery aptitude and vividness and body responsiveness did not predict accuracy. A second experiment tested whether embodiment could be responsible for the high level of effectiveness of the Body Scaffold; this was not supported. In short, mnemonic scaffolds are not equally effective and embodied cognition may not directly contribute to memory success. The Body Scaffold may be a strong alternative to the Method of Loci and may enhance learning for most learners, including those who do not find the Method of Loci useful.


Effect of teicoplanin and vancomycin on Staphylococcus aureus ultrastructure.
Morphological changes induced by teicoplanin and vancomycin on Staphylococcus aureus have been comparatively evaluated. The most pronounced structural damages were found on the cell wall which was uniformly thickened on bacteria exposed to teicoplanin while it was of irregular thickness and often absent around the cells in those exposed to vancomycin. The inhibitory action of teicoplanin on proteoglycan polymerization but not on nucleic acid and protein synthesis indicates that the effect in the wall is due to the accumulation at this level of proteoglycan soluble precursors continuously produced by the cell. The different effects induced by vancomycin on cell wall morphology can also be related to the compatibility of this antibiotic in altering cytoplasmatic membrane function and ribonucleic acid synthesis.


Histiocytic lymphoma fifteen years following remission of acute lymphoblastic leukemia.
A 19-yr-old female presented with diffuse histiocytic lymphoma after a 15-yr remission of acute lymphoblastic leukemia. All treatment had been discontinued 7 yr before the onset of the lymphoma. The possible relationships of these two neoplasms are discussed.


[Metformin-associated lactic acidosis].
The aims of this review are to precise the pathophysiological mechanisms leading to biguanide-associated lactic acidosis, to give elements of diagnosis, and to underline the precautionary conditions for prescribing these drugs by an improvement in physicians and patient's education. A PubMed database research in English and French language reports published until December 2005. The keywords were: lactic acidosis, metformin, biguanide, diabetes mellitus. Data in selected articles were reviewed, clinical and basic science research relevant informations were extracted. Metformin, which is an oral antidiabetic agent, is the only one biguanide available in France. It acts by enhancing the sensitivity to insulin by a decrease in the hepatic glucose production and an increase in its peripheral use. In term of glycemic control, it has the same efficiency than the other hypoglycemic agents. It represents the treatment of choice for overweight type 2 diabetic patients because of its beneficial effects on the weight loss and on the cardiovascular complications. The incidence of metformin-associated lactic acidosis is very low when contra-indications and appropriate rules for prescribing this drug are respected. The relationship between metformin and lactic acidosis remains largely controversial. In practical, we can distinguish three situations which have different prognosis. In the first case, metformin seems to be responsible for lactic acidosis because of self-poisoning or accidental overdose, and prognosis is good. In the second case, the association between metformin and lactic acidosis is coincidental rather than causal, and may be induced by an underlying organ failure. In the last case there is a cause of lactic acidosis which is worsened by a precipitating factor leading to metformin accumulation. The 2 latter situations are very severe as mortality rate is about 50%. Symptomatic treatments and renal replacement therapy which allows metformin removal are the curative treatment. Prevention is essential. It requires the respect of metformin contraindications and a better education of physicians and patients for a safe prescription. Due to its beneficial effects, metformin is the gold standard treatment for overweight type 2 diabetic patients. The essential precautionary conditions for prescribing metformin as well as the respect of its contra-indications permit largely to prevent lactic acidosis. This complication is serious when it is associated with intercurrent illnesses and metformin accumulation. The curative treatment is based on renal replacement therapy. Prevention only rests on the respect of the contra-indications. Education of physicians and patients concerning the rules of prescription remains essential.


Adaptive controller for dynamic power and performance management in the virtualized computing systems.
Power and performance management problem in large scale computing systems like data centers has attracted a lot of interests from both enterprises and academic researchers as power saving has become more and more important in many fields. Because of the multiple objectives, multiple influential factors and hierarchical structure in the system, the problem is indeed complex and hard. In this paper, the problem will be investigated in a virtualized computing system. Specifically, it is formulated as a power optimization problem with some constraints on performance. Then, the adaptive controller based on least-square self-tuning regulator(LS-STR) is designed to track performance in the first step; and the resource solved by the controller is allocated in order to minimize the power consumption as the second step. Some simulations are designed to test the effectiveness of this method and to compare it with some other controllers. The simulation results show that the adaptive controller is generally effective: it is applicable for different performance metrics, for different workloads, and for single and multiple workloads; it can track the performance requirement effectively and save the power consumption significantly.


A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61.
Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms (VLTly) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.


Ionic mechanism of substance P actions on neurons in trigeminal root ganglia.
1. Responses of primary sensory neurons to substance P applications by perfusion were studied with intracellular recording techniques in in vitro slice preparations of trigeminal root ganglia (guinea pigs). Application of substance P in micromolar doses produced reversible depolarizations of 2-47 mV in 48 out of 64 neurons. The depolarizing influence facilitated repetitive spike discharge evoked by current-pulse injection. Evidence of desensitization was observed during prolonged or repeated applications of the peptide. 2. The responses to substance P were associated with decreased input resistance, although increased input resistance was observed in neurons where the resting membrane potential was compensated with DC injection. In single-electrode voltage-clamp (SEVC) recordings, substance P evoked an inward shift in the holding current and reduced an outwardly rectifying component in the I-V relationships. The reversal potential for the substance P response could not be determined. These results suggested that the perikaryal response to substance P has a complex ionic mechanism involving activation and deactivation of membrane conductances. 3. Substance P-induced depolarizations were greatly attenuated during perfusion with solutions that were deficient in [Na+] or [Mg2+] and were not significantly affected during perfusion with low-[Ca2+]-, CO2(+)-containing solutions. 4. In the voltage-clamp investigations, an inward current contributed to the substance P responses during combined application with the K(+)-channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). This current was not abolished by the inclusion of CsCl in the perfusing solution or by internal Cs+ application from the recording electrode, suggesting that an anomalous inward rectifier was not involved in the responses to substance P.(ABSTRACT TRUNCATED AT 250 WORDS)


Aripiprazole as augmentation therapy in bipolar patients with current minor or subsyndromal mood symptoms.
This study aims to evaluate the effectiveness of aripiprazole augmentation of maintenance treatment for bipolar disorder in patients with minor or subsyndromal mood episodes while on a stable dose of a mood stabiliser and/or antidepressant. All subjects had a diagnosis of bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders-4th Edition, Text Revision). Open-label aripiprazole was given over 8 weeks initially. The starting dose was 5 to 15 mg/day with a mean final dose of 11.5 mg (±4.6). Patients were assessed at weeks 0, 2, 4 and 8 with the Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Clinical Global Impression of Severity (CGI-S). Seventeen of 20 (85%) patients completed week 4, while 14 (70%) patients completed 8 weeks. For intention-to-treat data, there was a significant decrease in MADRS scores over the course of treatment, with a reduction of 6.40 points at endpoint (p < 0.0005). Improvement from baseline was significant at week 2 and remained through to week 8. Similarly, CGI-S scores significantly decreased over the course of study, but not YMRS scores. Aripiprazole was shown to be a modestly effective augmentation therapy for depressive symptoms in bipolar I and II in this small open-label study.


Co-catalytic Effects of CoS2 on the Activity of the MoS2 Catalyst for Electrochemical Hydrogen Evolution.
MoS2 is a promising material to replace the Pt catalyst in the electrochemical hydrogen evolution reaction (HER). It is well known that the activity of the MoS2 catalyst in the HER is significantly promoted by doping cobalt atoms. Recently, the Co-Mo-S phase, in which cobalt atoms decorate the edge positions of the MoS2 slabs, has been identified as a co-catalytic phase in the Co-doped MoS2 (Co-MoSx) with low Co content. Here, we report the effect of the incorporation of cobalt atoms in the chemical state of the Co-MoSx catalyst, which gives rise to the co-catalytic effect. Co-MoSx catalysts with various Co contents were prepared on carbon fiber paper by a simple hydrothermal process. On the Co-MoSx catalyst with high Co content (Co/Mo ≈ 2.3), a dramatically higher catalytic activity was observed compared to that for the catalyst with low Co content (Co/Mo ≈ 0.36). Furthermore, the co-catalytic phase in the Co-MoSx catalyst with the high Co content was found not to be the Co-Mo-S phase but was identified as CoS2 by Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and transmission electron microscopy. It is believed that CoS2 is an alternative choice to co-catalyze HER on MoS2-based catalysts.


Exposure to organophosphorus pesticides in Norwegian mothers and their children: Diurnal variability in concentrations of their biomarkers and associations with food consumption.
Several studies have suggested that exposure to organophosphorus (OP) pesticides is detrimental for health, and in particular for children where moderate doses may have a negative impact on the neurodevelopment. This study surveys levels of the 6 non-specific urinary metabolites (dialkyl phosphates (DAPs)) of OP pesticides in Norwegian mothers (n=48) and their children (n=54), and examines the diurnal variation in concentrations as well as associations with consumption of specific food products. The highest median concentration measured in urine was found for dimethyl thiophosphate (5.3 and 5.5ng/mLSG; specific gravity corrected) for both children and mothers, respectively, followed by diethyl phosphate (3.8 and 5.3ng/mLSG, respectively). The intra-class correlation coefficients of DAPs among mothers were moderate (0.49-0.68), and consumption of fruit explained between 8% and 55% of the variations in the mothers' and their children's urinary DAP concentrations.


Immunity and immune modulation in Trypanosoma cruzi infection.
Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.


Serum uric acid concentration is associated with early changes of glomerular filtration rate in patients with diabetes type 1 without increased albumin excretion.
The early loss of renal function in patients with type 1 diabetes may begin before proteinuria. Only 30% of patients with diabetes manifest overt proteinuria. According to the previous studies, increased urinary albumin excretion, which is considered a classic marker of progression of diabetic kidney disease, can regress to normal urine albumin excretion. The current studies conducted in patients with type 1 diabetes without increased urine albumin excretion showed that the uric acid concentration was an independent factor for the development of diabetic kidney disease. The aim of study was to assess the impact of uric acid concentration and to identify risk factors of the early glomerular filtration loss in patients with type 1 diabetes and normal urinary albumin excretion. 147 patients (61 women and 86 men) with type 1 diabetes without increased urine albumin excretion were analysed. GFR (gromerular filtration rate) was estimated based on the serum cystatin C concentration. Centile charts were used to determine the variation of uric acid concentration depending on GFR and gender. The mean value of the filtration rate for the study group was 117 ml/min/m2. The uric acid level above 90th percentile in relation to GFR was diagnosed in 8.2% of women and 0% of men, between 90th and 50th percentile in 44.3 % of women and 5.8% of men and below 50th percentile in 47.5% of women and 94.2% of men. Contrary to men in women higher serum acid concentration was strongly associated with higher glomerular filtration rate. Hyperfiltraion was diagnosed in 15 of women and 19 of men. The high normal uric acid concentration in women with type 1 diabetes might play a crucial role in development of hyperfiltration.


COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate.
Preliminary data on coexistence of secondary hemophagocytic lymphohistiocytosis syndrome (HLH) and disseminated intravascular coagulation (DIC) in critically ill children with novel coronavirus disease (COVID-19) are emerging. Herein, we summarize the available literature and fill-in the gaps in this regard. We have performed a literature search for articles in PubMed, EMBASE and Google Scholar databases till May 12, 2020, with following keywords: "COVID-19", "SARS-CoV-2", "HLH", "HScore", "coagulopathy", "D-dimer", "cytokine storm", "children" and "pediatrics" with interposition of Boolean operator "AND". Children presenting with moderate-severe COVID-19 and Kawasaki disease shock-like syndrome exhibit peripheral blood picture analogous to HLH. HScore, a validated tool to diagnose HLH, has been suggested to screen severe COVID-19 patients for cytokine storm. However, HScore faces certain limitations in this scenario. It may be more pragmatic to use 'high D-dimer' (> 3 µg/mL) instead of 'low fibrinogen' to facilitate early detection of cytokine storm. COVID-19 associated coagulopathy resembles hypercoagulable form of DIC with bleeding being rarely reported. Although the International Society on Thrombosis and Haemostasis (ISTH) interim guidance recommends low molecular weight heparin in all hospitalized patients, data is lacking in population below 14 years of age. However, in the presence of life-threatening thromboembolic event or symptomatic acro-ischemia, unfractionated heparin (UFH) should be used with caution. HScore can be used as a complement to clinical decision for initiating immunosuppression. Children with moderate-to-severe COVID-19, especially those with documented thrombocytopenia or chilblains, should be regularly monitored for coagulopathy.


PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and Depolymerization.
PALLD is an actin cross-linker supporting cellular mechanical tension. However, its involvement in the regulation of phagocytosis, a cellular activity essential for innate immunity and physiological tissue turnover, is unclear. We report that PALLD is highly induced along with all-trans-retinoic acid-induced maturation of myeloid leukemia cells, to promote Ig- or complement-opsonized phagocytosis. PALLD mechanistically facilitates phagocytic receptor clustering by regulating actin polymerization and c-Src dynamic activation during particle binding and early phagosome formation. PALLD is also required at the nascent phagosome to recruit phosphatase oculocerebrorenal syndrome of Lowe, which regulates phosphatidylinositol-4,5-bisphosphate hydrolysis and actin depolymerization to complete phagosome closure. Collectively, our results show a new function for PALLD as a crucial regulator of the early phase of phagocytosis by elaborating dynamic actin polymerization and depolymerization.


Nonadiabatic response model of laser-induced ultrafast pi-electron rotations in chiral aromatic molecules.
We theoretically investigated the nonadiabatic couplings between optically induced pi-electron rotations and molecular vibrations in a chiral aromatic molecule irradiated by a nonhelical, linearly polarized laser pulse. The results of wave packet dynamics simulation show that the vibrational amplitudes strongly depend on the initial rotation direction, clockwise or counterclockwise, which is controlled by the polarization direction of the incident pulse. This suggests that attosecond pi-electron rotations can be observed by spectroscopic detection of femtosecond molecular vibrations.


Quantitative Systems Pharmacology Model of a Masked, Tumor-Activated Antibody.
PROBODY therapeutics (Pb-Tx) are protease-activatable prodrugs of monoclonal antibodies (mAbs) designed to target tumors where protease activity is elevated while avoiding normal tissue. They are composed of a parental mAb, a mask that inhibits antibody binding to target, and a protease-cleavable substrate between the mask and the mAb. We report a quantitative systems pharmacology model for the rational design and clinical translation of Pb-Tx. The model adequately described monkey pharmacokinetic data following the administration of six anti-CD166 Pb-Tx of varying mask strength and substrate cleavability and captured the trend of decreasing Pb-Tx systemic clearance with increasing mask strength. Projections to humans suggested both higher levels of Pb-Tx in tumor relative to parental mAb and an optimal mask strength for maximizing tumor receptor-mediated uptake. Simulations further suggested the majority of circulating species in humans would be intact/masked Pb-Tx, with no significant flux of cleaved/activated species from tumor to the systemic compartment.


Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.
Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.


A meta-ethnographic synthesis of midwives' and nurses' experiences of adverse labour and birth events.
Health professionals are frequently exposed to traumatic events due to the nature of their work. While traumatic and adverse labour and birth events experienced by women are well researched, less attention has been given to midwives' and nurses' experiences of these events and the impact it has on their lives. To undertake a meta-ethnographic study of midwives' and nurses' experiences of adverse labour and birth events. Scopus, CINHAL PLUS, MEDLINE and PUBMED databases were searched using subject headings and keywords. The search was limited to papers published in peer-reviewed journals from 2004-October 2016. Quality appraisal was undertaken using the Critical Appraisal Skills Programme tool. Papers had to be qualitative or have a substantial qualitative component. Studies were included if they primarily focused on midwives' or nurses' perspectives or experiences of complicated, traumatic or adverse labour and birth events. A meta-ethnographic approach was used incorporating methods of reciprocal translation guided by the work of Noblit and Hare (1988, Meta-Ethnography: Synthesizing qualitative studies (Vol. 11). Newbury Park: Sage publications). Eleven qualitative studies were included in the final sample. Four major themes were (i) feeling the chaos; (ii) powerless, responsible and a failure; (iii) "It adds another scar to my soul"; and (iv) finding a way to deal with it. Midwives and nurses feel relatively unprepared when faced with a real-life labour and birth emergency event. While many of the midwives and nurses were traumatised by the experience, some were able to view their encounter as an opportunity to develop their emergency response skills. Witnessing and being involved in a complicated or adverse labour and birth event can be traumatic for nurses and midwives. Organisational and collegial support needs to be available to enable these health professionals to talk about their feelings and concerns.


Cardiac screening for pregnant intravenous drug abusers.
We performed screening two-dimensional and M-mode echocardiograms on 23 pregnant intravenous drug abusers who had systolic murmurs that clinically appeared physiologic. Although no patient had symptoms or a history of cardiac disease, all but two of the women were evaluated as having unexpected cardiac valvular changes. The majority of morphologic valvular findings on echocardiography consisted of either a mitral valve prolapse or valvular leaflet thickening. However, two of these 21 women were identified as having a previously undiagnosed aortic or tricuspid vegetation for which they subsequently received prophylactic antibiotic therapy during labor and delivery. Notably, two additional women among the group with morphologic valvular changes ultimately developed subacute bacterial endocarditis. Atypically, the clinical illness occurred antenatally for one of the two women with a mitral valve prolapse and 18 months postpartum for another women with unexplained valvular thickening. On the basis of these observations, a more liberal use of echocardiography in the care of the pregnant intravenous drug abuser population is suggested for evaluation of otherwise seemingly innocuous systolic murmurs.


Comparison of APACHE II and SAPS II Scoring Systems in Prediction of Critically Ill Patients' Outcome.
Using physiologic scoring systems for identifying high-risk patients for mortality has been considered recently. This study was designed to evaluate the values of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiologic Score (SAPS II) models in prediction of 1-month mortality of critically ill patients. The present prospective cross sectional study was performed on critically ill patients presented to emergency department during 6 months. Data required for calculation of the scores were gathered and performance of the models in prediction of 1-month mortality were assessed using STATA software 11.0. 82 critically ill patients with the mean age of 53.45 ± 20.37 years were included (65.9% male). Their mortality rate was 48%. Mean SAPS II (p < 0.0001) and APACHE II (p = 0.0007) scores were significantly higher in dead patients. Area under the ROC curve of SAPS II and APACHE II for prediction of mortality were 0.75 (95% CI: 0.64 - 0.86) and 0.72 (95% CI: 0.60 - 0.83), respectively (p = 0.24). The slope and intercept of SAPS II were 1.02 and 0.04, respectively. In addition, these values were 0.92 and 0.09 for APACHE II, respectively. The findings of the present study showed that APACHE II and SAPS II had similar value in predicting 1-month mortality of patients. Discriminatory powers of the mentioned models were acceptable but their calibration had some amount of lack of fit, which reveals that APACHE II and SAPS II are partially perfect.


Selected comorbidities of atopic dermatitis: Atopy, neuropsychiatric, and musculoskeletal disorders.
Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease with substantial morbidity and quality of life impairment. There are a number of comorbid health problems that occur in patients with AD, aside from the cutaneous signs and symptoms. Chronic pruritus and inflammation can lead to sleep disturbances and mental health symptoms, which are not mutually exclusive. AD is associated with and may predispose to higher risk of other atopic disorders, including asthma and hay fever. Persons with AD appear to be at higher risk for multiple neuropsychiatric disorders, including depression, attention-deficit/hyperactivity disorder, speech disorders in childhood, headaches, and seizures. There is also a multifactorial association of AD with osteoporosis, injuries, and fractures. Elucidating the comorbidities of AD is important for disease management and improving overall clinical outcomes. This review summarizes recent developments in the atopic and neuropsychiatric comorbidities of AD.


Role of chondrocyte death and hypocellularity in ageing human articular cartilage and the pathogenesis of osteoarthritis.
Apoptotic death of articular chondrocytes has been implicated in the pathogenesis of human osteoarthritis. Although nitric oxide and Fas ligand have been shown to be inducers of chondrocyte apoptosis in vitro and in vivo, the contribution of other triggers such as hypoxia, matrix acidosis, abnormal shear stress and catabolic cytokines like interleukin-1beta and tumour necrosis factor alpha has not been examined. It is also not known if growth factors such as insulin like growth factor 1 or anabolic cytokines prevent apoptosis. The intracellular mechanism of effecting apoptotic death depend on whether damage to the mitochondrion or receptor ligation is the primary apoptotic stimulus, since these activate different initiator caspases which then deliver the apoptotic signal to common downstream effector caspases and other proteases. The hypothesis proposed here suggests that by using chondrocytes derived from control and osteoarthritis joints and established human chondrocyte cell lines, it is possible to investigate the relative contributions of major cell death inducing mechanisms and correspondingly which initiating caspase is activated. This understanding is essential for developing appropriately targeted anti-protease therapies for the inhibition of chondrocyte apoptosis in the rational treatment of osteoarthritis.


Mitochondrial protein transport: Versatility of translocases and mechanisms.
Biogenesis of mitochondria requires the import of approximately 1,000 different precursor proteins into and across the mitochondrial membranes. Mitochondria exhibit a wide variety of mechanisms and machineries for the translocation and sorting of precursor proteins. Five major import pathways that transport proteins to their functional intramitochondrial destination have been elucidated; these pathways range from the classical amino-terminal presequence-directed pathway to pathways using internal or even carboxy-terminal targeting signals in the precursors. Recent studies have provided important insights into the structural organization of membrane-embedded preprotein translocases of mitochondria. A comparison of the different translocases reveals the existence of at least three fundamentally different mechanisms: two-pore-translocase, β-barrel switching, and transport cavities open to the lipid bilayer. In addition, translocases are physically engaged in dynamic interactions with respiratory chain complexes, metabolite transporters, quality control factors, and machineries controlling membrane morphology. Thus, mitochondrial preprotein translocases are integrated into multi-functional networks of mitochondrial and cellular machineries.